一项初步研究调查了对侵袭性三阴性乳腺癌（TNBC）的免疫疗法策略，发现了参与胞外囊泡（EVs）释放的基因的过表达。 EVs表达的蛋白质在重编程肿瘤微环境和阻碍免疫疗法的有效响应方面起作用。在乳腺癌细胞的胞外空间中发现的半乳糖凝集素3（Gal3）下调T细胞受体的表达。 Gal3与包括CD45在内的几种受体结合，CD45是T细胞受体激活所需的。我们先前报道了一种新的肿瘤逃逸机制，即通过CD45细胞内信号，TNBC细胞通过CD45内细胞信号抑制免疫细胞。本研究的目标是确定Gal3与TNBC分泌的EVs通过CD45信号通路诱导免疫抑制之间的潜在关联。从MDA-MB-231细胞和TNBC患者的血浆中分离出EVs。质谱分析揭示了在分离的小型EVs中存在Gal3结合蛋白（Gal3BP），它与TNBC分泌的Gal3相互作用。 Gal3BP和Gal3形成的复合物会显著增加外周血单个核细胞（PBMCs）中的调节性T细胞数量。这种增加与抑制性白介素10和35的显著增加相关。在与肿瘤来源的EVs一起培养的PBMCs中阻断CD45受体可以阻止Gal3BP / Gal3复合物对免疫抑制的作用。这导致IFN-γ的增加和CD4、CD8和CD56效应细胞的活化。本研究提出了一种肿瘤逃逸机制，可能有助于针对TNBC开发与当前疗法相辅相成的不同免疫疗法策略。 © 2023 The Author（s）。Published with license by Taylor & Francis Group, LLC.

A preliminary study investigating immunotherapy strategies for aggressive triple negative breast cancer (TNBC) revealed an overexpression of genes involved in the release of extracellular vesicles (EVs). Proteins expressed by EVs play a role in reprogramming the tumor microenvironment and impeding effective responses to immunotherapy. Galectin 3 (Gal3), found in the extracellular space of breast cancer cells, downregulates T-cell receptor expression. Gal3 binds to several receptors, including CD45, which is required for T-cell receptor activation. Previously, we reported a novel tumor escape mechanism, whereby TNBC cells suppress immune cells through CD45 intracellular signals. The objective of this study was to determine the potential association of Gal3 with TNBC-secreted EVs induction of immunosuppression via the CD45 signaling pathway. EVs were isolated from MDA-MB-231 cells and the plasma of patients with TNBC. Mass spectrometry revealed the presence of Gal3 binding protein (Gal3BP) in the isolated small EVs, which interacted with TNBC secreted Gal3. Gal3BP and Gal3 form a complex that induces a significant increase in T-regulatory cells in peripheral blood mononuclear cells (PBMCs). This increase correlates with a significant increase in suppressive interleukins 10 and 35. Blocking the CD45 receptor in PBMCs cultured with tumor-derived EVs impeded the immunosuppression exerted by the Gal3BP/Gal3 complex. This led to an increase in IFN-γ and the activation of CD4, CD8 and CD56 effector cells. This study suggests a tumor escape mechanism that may contribute to the development of a different immunotherapy strategy that complements current therapies used for TNBC.© 2023 The Author(s). Published with license by Taylor & Francis Group, LLC.